Structural covariance and cortical reorganisation in schizophrenia: a MRI-based morphometric study.

BACKGROUND: In patients with schizophrenia, distributed abnormalities are observed in grey matter volume. A recent hypothesis posits that these distributed changes are indicative of a plastic reorganisation process occurring in response to a functional defect in neuronal information transmission. We investigated the structural covariance across various brain regions in early-stage schizophrenia to determine if indeed the observed patterns of volumetric loss conform to a coordinated pattern of structural reorganisation. METHODS: Structural magnetic resonance imaging scans were obtained from 40 healthy adults and 41 age, gender and parental socioeconomic status matched patients with schizophrenia. Volumes of grey matter tissue were estimated at the regional level across 90 atlas-based parcellations. Group-level structural covariance was studied using a graph theoretical framework. RESULTS: Patients had distributed reduction in grey matter volume, with high degree of localised covariance (clustering) compared with controls. Patients with schizophrenia had reduced centrality of anterior cingulate and insula but increased centrality of the fusiform cortex, compared with controls. Simulating targeted removal of highly central nodes resulted in significant loss of the overall covariance patterns in patients compared with controls. CONCLUSION: Regional volumetric deficits in schizophrenia are not a result of random, mutually independent processes. Our observations support the occurrence of a spatially interconnected reorganisation with the systematic de-escalation of conventional 'hub' regions. This raises the question of whether the morphological architecture in schizophrenia is primed for compensatory functions, albeit with a high risk of inefficiency.

Cortical folding and the potential for prognostic neuroimaging in schizophrenia.

In 41 patients with schizophrenia, we used neuroanatomical information derived from structural imaging to identify patients with more severe illness, characterised by high symptom burden, low processing speed, high degree of illness persistence and lower social and occupational functional capacity. Cortical folding, but not thickness or volume, showed a high discriminatory ability in correctly identifying patients with more severe illness.

Regional Brain Correlates of Beta Bursts in Health and Psychosis: A Concurrent Electroencephalography and Functional Magnetic Resonance Imaging Study.

BACKGROUND: There is emerging evidence for abnormal beta oscillations in psychosis. Beta oscillations are likely to play a key role in the coordination of sensorimotor information that is crucial to healthy mental function. Growing evidence suggests that beta oscillations typically manifest as transient beta bursts that increase in probability following a motor response, observable as post-movement beta rebound. Evidence indicates that post-movement beta rebound is attenuated in psychosis, with greater attenuation associated with greater symptom severity and impairment. Delineating the functional role of beta bursts therefore may be key to understanding the mechanisms underlying persistent psychotic illness. METHODS: We used concurrent electroencephalography and functional magnetic resonance imaging to identify blood oxygen level-dependent correlates of beta bursts during the n-back working memory task and intervening rest periods in healthy control participants (n = 30) and patients with psychosis (n = 48). RESULTS: During both task blocks and intervening rest periods, beta bursts phasically activated regions implicated in task-relevant content while suppressing currently tonically active regions. Patients showed attenuated post-movement beta rebound that was associated with persisting disorganization symptoms as well as impairments in cognition and role function. Patients also showed greater task-related reductions in overall beta burst rate and showed greater, more extensive, beta burst-related blood oxygen level-dependent activation. CONCLUSIONS: Our evidence supports a model in which beta bursts reactivate latently maintained sensorimotor information and are dysregulated and inefficient in psychosis. We propose that abnormalities in the mechanisms by which beta bursts coordinate reactivation of contextually appropriate content can manifest as disorganization, working memory deficits, and inaccurate forward models and may underlie a core deficit associated with persisting symptoms and impairment.

Speech structure links the neural and socio-behavioural correlates of psychotic disorders.

BACKGROUND: A longstanding notion in the concept of psychosis is the prominence of loosened associative links in thought processes. Assessment of such subtle aspects of thought disorders has proved to be a challenging task in clinical practice and to date no surrogate markers exist that can reliably track the physiological effects of treatments that could reduce thought disorders. Recently, automated speech graph analysis has emerged as a promising means to reliably quantify structural speech disorganization. METHODS: Using structural and functional imaging, we investigated the neural basis and the functional relevance of the structural connectedness of speech samples obtained from 56 patients with psychosis (22 with bipolar disorder, 34 with schizophrenia). Speech structure was assessed by non-semantic graph analysis. RESULTS: We found a canonical correlation linking speech connectedness and i) functional as well as developmentally relevant structural brain markers (degree centrality from resting state functional imaging and cortical gyrification index) ii) psychometric evaluation of thought disorder iii) aspects of cognitive performance (processing speed deficits) and iv) functional outcome in patients. Of various clinical metrics, only speech connectedness was correlated with biological markers. Speech connectedness filled the dynamic range of responses better than psychometric measurements of thought disorder. CONCLUSIONS: The results provide novel evidence that speech dysconnectivity could emerge from neurodevelopmental deficits and associated dysconnectivity in psychosis.

Abnormalities in structural covariance of cortical gyrification in schizophrenia.

The highly convoluted shape of the adult human brain results from several well-coordinated maturational events that start from embryonic development and extend through the adult life span. Disturbances in these maturational events can result in various neurological and psychiatric disorders, resulting in abnormal patterns of morphological relationship among cortical structures (structural covariance). Structural covariance can be studied using graph theory-based approaches that evaluate topological properties of brain networks. Covariance-based graph metrics allow cross-sectional study of coordinated maturational relationship among brain regions. Disrupted gyrification of focal brain regions is a consistent feature of schizophrenia. However, it is unclear if these localized disturbances result from a failure of coordinated development of brain regions in schizophrenia. We studied the structural covariance of gyrification in a sample of 41 patients with schizophrenia and 40 healthy controls by constructing gyrification-based networks using a 3-dimensional index. We found that several key regions including anterior insula and dorsolateral prefrontal cortex show increased segregation in schizophrenia, alongside reduced segregation in somato-sensory and occipital regions. Patients also showed a lack of prominence of the distributed covariance (hubness) of cingulate cortex. The abnormal segregated folding pattern in the right peri-sylvian regions (insula and fronto-temporal cortex) was associated with greater severity of illness. The study of structural covariance in cortical folding supports the presence of subtle deviation in the coordinated development of cortical convolutions in schizophrenia. The heterogeneity in the severity of schizophrenia could be explained in part by aberrant trajectories of neurodevelopment.

Structural correlates of formal thought disorder in schizophrenia: An ultra-high field multivariate morphometry study.

BACKGROUND: Persistent formal thought disorder (FTD) is one of the most characteristic features of schizophrenia. Several neuroimaging studies report spatially distinct neuroanatomical changes in association with FTD. Given that most studies so far have employed a univariate localisation approach that obscures the study of covarying interregional relationships, the present study focussed on the multivariate systemic pattern of anatomical changes that contribute to FTD. METHODS: Speech samples from nineteen medicated clinically stable schizophrenia patients and 20 healthy controls were evaluated for subtle formal thought disorder. Ultra high-field (7T) anatomical Magnetic Resonance Imaging scans were obtained from all subjects. Multivariate morphometric patterns were identified using an independent component approach (source based morphometry). Using multiple regression analysis, the morphometric patterns predicting positive and negative FTD scores were identified. RESULTS: Morphometric variations in grey matter predicted a substantial portion of inter-individual variance in negative but not positive FTD. A pattern of concomitant striato-insular/precuneus reduction along with frontocingular grey matter increase had a significant association with negative FTD. CONCLUSIONS: These results suggest that concomitant increase and decrease in grey matter occur in association with persistent negative thought disorder in clinically stable individuals with schizophrenia.

The neuroanatomy of psychotic diathesis: a meta-analytic review.

BACKGROUND: Several studies have found widespread structural changes affecting the grey matter at various stages of schizophrenia (the prodrome, first-episode, and the chronic stage). It is unclear which of these neuroanatomical changes are associated with a predisposition or vulnerability to develop schizophrenia rather than the appearance of the clinical features of the illness. METHODS: 16 voxel-based morphometry (VBM) analyses involving 733 genetically high-risk relatives (HRR) of patients with schizophrenia, 563 healthy controls and 474 patients were meta-analysed using the Signed Differential Mapping (SDM) technique. Two meta-analyses were conducted, with one comparing HRR group with healthy controls and the other comparing HRR group with the patients. RESULTS: A significant grey matter reduction in the lentiform nucleus, amygdala/parahippocampal gyrus and medial prefrontal cortex was seen in association with the genetic diathesis. Grey matter reduction in bilateral insula, inferior frontal gyrus, superior temporal gyrus and the anterior cingulate was seen in association with the disease expression. CONCLUSIONS: The neuroanatomical changes associated with the genetic diathesis to develop schizophrenia appear to be different from those that contribute to the clinical expression of the illness. Grey matter abnormalities in multimodal brain regions that have a supervisory function are likely to be central to the expression of the clinical symptoms of schizophrenia.

Structural correlates of auditory hallucinations in schizophrenia: a meta-analysis.

BACKGROUND: Despite being one of the most common symptoms of schizophrenia, determining the neural correlates of auditory hallucinations still remains elusive with various studies providing inconsistent results. METHODS: We conducted a voxel-based meta-analysis of studies investigating the structural correlates of auditory hallucinations in schizophrenia. RESULTS: 7 datasets including 350 patients were identified. There was a significant negative correlation between the severity of hallucinations and gray matter volume in the left insula and right superior temporal gyrus. CONCLUSION: With its key role in stimulus evaluation and optimizing prediction (proximal salience), the insula is likely to be a cardinal region along with superior temporal gyrus in the mechanism of auditory hallucinations in schizophrenia.